The invention relates to an assay device processing instrument, for example for processing assay devices in the form of chips on which have been deposited an array of localised reactive sites containing different reactive species, for example different antibodies.
In this context, xe2x80x9cassayxe2x80x9d means the quantitative analysis of a substance to determine the proportion of some valuable or potent constituent e.g. the active constituent in a pharmaceutical.
An immunoassay is a technique which measures the presence of a substance (analyte) in a biological sample exploiting an immunological reaction between antibody and antigen.
In the fields of chemical/veterinary diagnosis or drug screening, it is necessary to analyse samples to determine the presence of certain analytes. Recently, it has been proposed to provide a set of different antibodies on respective reactive sites on a substrate such as a chip. The sample is deposited on the chip and following incubation and other processes, a chemiluminescence process is monitored to detect the presence or absence of the appropriate analyte at each site. This is described in more detail in EP-A-0902394.
The problem with analysis of such chips is that the processes are complex and require careful handling of the chips and thus significant manual intervention.
WO-A-93/23732 describes automatic staining apparatus for slide specimens but this is a histochemical process and has no relevance to assays.
In accordance with one aspect of the present invention, an assay device processing instrument comprises a plurality of assay device processing modules; a transport system including an assay device positioning assembly for transporting an assay device to each processing module, the assay device positioning assembly being adapted to transfer the assay device to each module to enable the assay device positioning assembly to transport another assay device while the transferred assay device(s) is processed; and a control system for controlling operation of the transport system such that each assay device is transferred between the modules in a predetermined sequence, and such that a number of assay devices can be processed in different modules simultaneously.
We have realised that it is possible to develop a sophisticated multi-tasking processing instrument by developing a transport system which can transport an assay device to a processing module and transfer the assay device to the module thus releasing the transport system to transport another assay device while the first is processed. Under computer control, a large number of assay devices could be processed simultaneously with such an instrument.
A variety of transport systems could be used. In one case a rotary transport system could be implemented which will be relatively compact. The simplest rotary system would involve a circular xe2x80x9cshaftxe2x80x9d, and an assay device positioning assembly mounted for movement about the shaft, the shaft rotating until the positioning assembly is aligned with the respective processing module entry point for input or extraction of the storage units.
More complex options would involve rotating concentric assemblies/modules. The inner module could act as an incubator/shaker with the outer ring being the transport system. Thus, for example the incubator/shaker could shake with small angular movements about the vertical axis/shaft. The incubator/shaker could be multi-level/stack.
The storage units may be pushed out/pulled in between the inner incubator/shaker and the outer transport system via e.g. a push/pull motor assembly located within the centre of the inner incubator xe2x80x9cringxe2x80x9d.
In the preferred example, the transport system comprises a rail; an assay device positioning assembly mounted for movement along the rail; and a first motor responsive to the control system to move the assay device positioning assembly into alignment with the respective processing modules. Preferably, the rail is linear. This increases the simplicity and ease of design and modification of such a system over, for example, a rotary system.
In some cases, the transport system can be folded back on itself into a multi-plane system thus forming a more compact design than one which is based on a single plane.
In some cases, part of the transport system at each module could include means for transferring an assay device to and from the module. However, a simpler and preferred approach is to provide the transport system with a support movably mounted to the rail; an arm for engaging an assay device and movably mounted to the support for movement laterally relative to the rail; and a second motor on the support for causing lateral movement of the arm. In this case, the arm for moving the assay device moves with the support along the rail so that only a single such arm is required. Typically, the arm will move relative to the support substantially orthogonally to the rail although this is not essential.
Conveniently, the arm has means for gripping the assay device although in other cases, the arm could simply push the assay device to different positions or connect to it by other means such as a magnetic coupling.
Preferably, however, the assay device is supported in an assay device holder having a formation which cooperates releasably with the gripping means to enable the assay device to be positioned by the arm. Such an arrangement is described in more detail in EP Patent Application No. 98307732.2.
A variety of modules could be provided. Typically, they will include one or more of:
a) a buffer for storing more than one assay device or assay device holder;
b) an incubator;
c) a wash station; and,
d) an assay device imaging station.
The use of a buffer is helpful in that it allows reactions to take place which require a period of time during which other assay devices can be transported and subjected to other processes. Conveniently, however, the buffer is provided by the incubator. Since assay devices normally have to be retained within the incubator for a period of time, this provides a useful dual purpose as a buffer.
An imaging station is needed in order to view the reaction sites after processing and it is important to restrict the access of ambient light. It is therefore necessary for the imaging station to be closed during the imaging process. This could be achieved by separately operating a door through which the assay device passes. This process can be simplified when the imaging station includes an entrance door which is automatically activated during transfer of the assay device to and from the imaging station.
This automatic activation could be achieved using sensors and the like to monitor movement of the assay device and a system responsive to the sensors to open the door. However, preferably the door is pivoted about an upper, horizontal axis to a wall of the imaging station and is coupled to a movable platform of the imaging station by a link pivoted to both the platform and the door whereby movement of the platform towards the door from either side of the door, causes the door to open and thereafter close once the platform has passed through from one side to the other.
As mentioned above, an important module for use during an immunoassay process is an incubator. In addition, it is usually necessary to shake or vibrate the assay device to promote the chemical reactions which are to take place.
Some examples of incubators are described in xe2x80x9cEnvironmental Shakers/Incubatorsxe2x80x9d by Shane Beck, Aug. 17, 1998. However, these are relatively unsophisticated.
In accordance with a second aspect of the present invention, an assay device incubator comprises a housing and a set of assay device supports positioned within the housing; means for independently heating each assay device within the housing; and means for shaking the support relative to the housing.
Unlike other systems, this new incubator enables shaking, incubation and accurate, independent heating control to be carried out at the same time so that no transfer is required between separate shaking and incubating modules during the reaction period.
Preferably, the frequency of the shaking means is variable while the stroke may be constant or variable. The stroke could be a simple to and fro horizontal motion, a vertical motion, an orbital motion or any combination of these. Typically, the type of motion will be chosen to optimize mixing procedures and speed of reaction. Additionally, periodic stops may be included in the shaking process to optimize reaction.
Although the transport system could be adjustable to load assay devices into appropriate locations within the incubator, when the supports are located in different vertical positions within a support unit, the support unit is preferably vertically movable to bring a selected support into alignment with the instrument transport system.
A further module which is used in an assay process such as an immunoassay process is a washing module. Conventionally, such modules include a probe for delivering wash fluid and an aspirator probe for removing wash fluid.
In accordance with a third aspect of the present invention, we provide an assay device washing module for washing an assay device located within an assay device well holder, the module comprising a wash fluid delivery probe and an aspirator probe mounted to a movable support, the aspirator probe being mounted at an angle to the vertical and the support being movable at substantially the same angle whereby when the aspirator probe is inserted into a well holder it is brought close to the side of the well holder.
This new washing module improves the aspiration of fluid from the well holder by directing the aspirator probe at an angle so that it is brought close to the side of the well holder and hence adjacent the channel which is formed between the assay device and the well holder. This then completely avoids any risk of contact with the active area and damage to the assay device while achieving significantly better aspiration since fluid is drawn from the channel around the assay device.
It is necessary to wash the probes between each assay device wash operation so preferably a probe wash region is located beneath the wash location of the well holder, the support being movable, in the absence of a well holder, to bring the aspirator probe into the wash region. This provides a convenient way of washing the probes while maintaining automatic operation of the washing module.
Preferably, the module further comprises a vacuum supply system coupled to the aspirator probe, the vacuum supply system including a vacuum vessel having a first port connected to a vacuum source, a second port connected to the aspirator probe and a third port connected to a drain via a drain pump.